PMID- 34953963
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220531
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 153
DP  - 2022 Feb
TI  - Activation of vitamin D receptor inhibits Tau phosphorylation is associated with 
      reduction of iron accumulation in APP/PS1 transgenic mice.
PG  - 105260
LID - S0197-0186(21)00306-5 [pii]
LID - 10.1016/j.neuint.2021.105260 [doi]
AB  - Vitamin D deficiency and iron accumulation are prevalent in the brains of 
      Alzheimer's disease (AD) patients, however, whether Vitamin D has a role in the 
      regulations of iron metabolism in the condition of AD remains unknown. Our 
      previous studies revealed that vitamin D deficiency promotes beta-amyloid (Abeta) 
      deposition in the APP/PS1 mouse brains, while supplemented with a specific 
      agonist of vitamin D receptor (VDR), paricalcitol (PAL), significantly reduced Abeta 
      production via promoting the lysosomal degradation of beta-site APP cleavage enzyme 
      1 (BACE1). In this study, our data suggested that activation of VDR by PAL 
      significantly reduced the iron accumulation in the cortex and hippocampus of 
      APP/PS1 mice through downregulation of Transferrin receptor (TFR) by reducing 
      iron-regulatory protein 2 (IRP2) expression. Furthermore, activation of VDR 
      effectively reduced the phosphorylations of Tau at Ser396 and Thr181 sites via 
      inhibiting the GSK3beta phosphorylation (Tyr216). Taken together, our data suggest 
      that activation of VDR could inhibit the phosphorylations of Tau possibly by 
      repressing the iron accumulation-induced upregulation of GSK3beta activity in the 
      brains of APP/PS1 mice. Thus, activation of VDR may be an effective strategy for 
      treating AD.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Wu, Ting-Yao
AU  - Wu TY
AD  - First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China. 
      Electronic address: llhfyg@163.com.
FAU - Zhao, Ling-Xiao
AU  - Zhao LX
AD  - Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry 
      of Education, China Medical University, Shenyang, 110122, China.
FAU - Zhang, Yan-Hui
AU  - Zhang YH
AD  - Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry 
      of Education, China Medical University, Shenyang, 110122, China.
FAU - Fan, Yong-Gang
AU  - Fan YG
AD  - Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry 
      of Education, China Medical University, Shenyang, 110122, China. Electronic 
      address: ygfan@cmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211222
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Presenilin-1)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Vdr protein, mouse)
RN  - 0 (tau Proteins)
RN  - E1UOL152H7 (Iron)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
SB  - IM
MH  - *Alzheimer Disease/drug therapy/metabolism
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Aspartic Acid Endopeptidases
MH  - Humans
MH  - Iron
MH  - Mice
MH  - Mice, Transgenic
MH  - Phosphorylation
MH  - Presenilin-1/genetics
MH  - *Receptors, Calcitriol/metabolism
MH  - *tau Proteins/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Iron accumulation
OT  - Tau phosphorylation
OT  - Vitamin D receptor
EDAT- 2021/12/27 06:00
MHDA- 2022/03/17 06:00
CRDT- 2021/12/26 20:34
PHST- 2021/09/13 00:00 [received]
PHST- 2021/11/29 00:00 [revised]
PHST- 2021/12/21 00:00 [accepted]
PHST- 2021/12/27 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/12/26 20:34 [entrez]
AID - S0197-0186(21)00306-5 [pii]
AID - 10.1016/j.neuint.2021.105260 [doi]
PST - ppublish
SO  - Neurochem Int. 2022 Feb;153:105260. doi: 10.1016/j.neuint.2021.105260. Epub 2021 
      Dec 22.